{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc}} {{Infobox gene}}
'''Aldo-keto reductase family 1 member C2''', also known as '''bile acid binding protein''', '''3α-hydroxysteroid dehydrogenase type 3''' ('''3α-HSD3'''),<ref name="pmid24434280">{{cite journal | url=https://www.sciencedirect.com/science/article/pii/S0960076014000065 | doi=10.1016/j.jsbmb.2014.01.003 | title=Human 3-alpha hydroxysteroid dehydrogenase type 3 (3α-HSD3): The V54L mutation restricting the steroid alternative binding and enhancing the 20α-HSD activity | date=2014 | last1=Zhang | first1=Bo | last2=Zhu | first2=Dao-Wei | last3=Hu | first3=Xiao-Jian | last4=Zhou | first4=Ming | last5=Shang | first5=Peng | last6=Lin | first6=Sheng-Xiang | journal=The Journal of Steroid Biochemistry and Molecular Biology | volume=141 | pages=135–143 | pmid=24434280 | url-access=subscription }}</ref><ref name="pmid31610224">{{cite journal | url=https://www.sciencedirect.com/science/article/pii/S0960076019302699 | doi=10.1016/j.jsbmb.2019.105494 | title=Steroid enzyme and receptor expression and regulations in breast tumor samples – A statistical evaluation of public data | date=2020 | last1=Li | first1=Tang | last2=Zhang | first2=Wenfa | last3=Lin | first3=Sheng-Xiang | journal=The Journal of Steroid Biochemistry and Molecular Biology | volume=196 | article-number=105494 | pmid=31610224 | url-access=subscription | access-date=2024-04-08 | archive-date=2024-04-17 | archive-url=https://web.archive.org/web/20240417075146/https://www.sciencedirect.com/science/article/abs/pii/S0960076019302699 | url-status=live }}</ref> and '''dihydrodiol dehydrogenase type 2''', is an enzyme that in humans is encoded by the ''AKR1C2'' gene.<ref name="entrez">{{cite web | title = Entrez Gene: AKR1C2 aldo-keto reductase family 1, member C2 (dihydrodiol dehydrogenase 1; 20-alpha (3-alpha)-hydroxysteroid dehydrogenase) | publisher = National Center for Biotechnology Information, U.S. National Library of Medicine | url = https://www.ncbi.nlm.nih.gov/gene/1646 | archive-date = 2019-03-29 | archive-url = https://web.archive.org/web/20190329132306/https://www.ncbi.nlm.nih.gov/gene/1646 | url-status = live }} {{PD-notice}}</ref>
==Superfamily of enzymes== This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols using NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This particular enzyme, AKR1C2, binds bile acid with high affinity, and shows minimal 3α-hydroxysteroid dehydrogenase activity. The ''AKR1C2'' gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. Three transcript variants encoding two different isoforms have been found for this gene.<ref name="entrez"/> The AKR1C2 enzyme catalyzes reactions at specific positions on the steroid nucleus. Specifically, AKR enzymes, including AKR1C2, act as 3α/β-HSDs, 17β-HSDs, and 20α-HSDs, catalyzing NAD(P)(H)-dependent oxidoreduction of substituents at the C3, C17, and C20 positions of the steroid nucleus.<ref name="Feder-1981">{{cite book|doi=10.1007/978-1-4684-3875-8_3|isbn=978-1-4684-3875-8|year=1981 |chapter=Essentials of Steroid Structure, Nomenclature, Reactions, Biosynthesis, and Measurements |title=Neuroendocrinology of Reproduction |pages=19–63 | vauthors = Feder HH }}</ref><ref name="pmid30137266">{{cite journal|doi=10.1210/er.2018-00089|date = 20 August 2018 | title=Structural and Functional Biology of Aldo-Keto Reductase Steroid-Transforming Enzymes | journal=Endocrine Reviews | volume=40 | issue=2 | pages=447–475 | pmid=30137266 | pmc=6405412 | vauthors = Penning TM, Wangtrakuldee P, Auchus RJ }}</ref><ref name="pmid36827074">{{cite journal |vauthors=Zhou Y, Lin Y, Li W, Liu Q, Gong H, Li Y, Luo D |title=Expression of AKRs superfamily and prognostic in human gastric cancer |journal=Medicine (Baltimore) |volume=102 |issue=8 |article-number=e33041 |date=February 2023 |pmid=36827074 |doi=10.1097/MD.0000000000033041 |doi-access=free |pmc=11309706 }}</ref>
==Aldo-keto reductase activity== AKR1C2 binds bile acid with high affinity catalyzing aldo-keto reduction reaction.<ref name="entrez"/>
Aldo-keto reductases, including AKR1C2, are NAD(P)H-linked oxidoreductases that primarily catalyze the reduction of aldehydes and ketones to primary and secondary alcohols. This reduction is dependent on NADPH.<ref name="pmid28352233">{{cite journal |vauthors=Zeng CM, Chang LL, Ying MD, Cao J, He QJ, Zhu H, Yang B |title=Aldo-Keto Reductase AKR1C1-AKR1C4: Functions, Regulation, and Intervention for Anti-cancer Therapy |journal=Front Pharmacol |volume=8 |page=119 |date=14 March 2017 |pmid=28352233 |pmc=5349110 |doi=10.3389/fphar.2017.00119 |doi-access=free }}</ref><ref name="pmid22408622">{{cite journal |vauthors=Chen WD, Zhang Y |title=Regulation of aldo-keto reductases in human diseases |journal=Front Pharmacol |volume=3 |page=35 |date=9 March 2012 |pmid=22408622 |pmc=3297832 |doi=10.3389/fphar.2012.00035|doi-access=free }}</ref>
In the context of bile acids, the AKR1C2 enzyme would bind to the bile acid (a type of steroid molecule) and catalyze the reduction of a carbonyl group (C=O) present in the bile acid to a hydroxy group (-OH), using NADPH as a cofactor.<ref name="pmid28352233"/><ref name="pmid22408622"/> This reaction is part of the broader metabolic processes that these enzymes are involved in, which include biosynthesis, intermediary metabolism, and detoxification.<ref name="pmid28352233"/><ref name="pmid22408622"/>
==3α-hydroxysteroid dehydrogenase activity== The AKR1C2 enzyme is also known as 3α-hydroxysteroid dehydrogenase type 3 (3α-HSD3), meaning that the enzyme possesses 3α-hydroxysteroid dehydrogenase activity, i.e. it can hydroxylate steroids at a carbon position 3α of the steroid nucleus, attaching the hydroxy group (-OH) to carbon 3 in α stereiodirection. 3α-hydroxysteroid dehydrogenases, including AKR1C2, are NAD(P)H-linked oxidoreductases that primarily catalyze the oxidation of 3α-hydroxysteroids to their corresponding 3-ketosteroids. This oxidation is dependent on NAD+. The substrates for the 3α-HSD3 enzyme are steroids such as androgens, estrogens, and progestins, which regulate various sex functions. For example, 3α-HSD3 can catalyze the conversion of the potent androgen 5α-dihydrotestosterone (DHT) into its much less active form, 5α-androstan-3α,17β-diol (3α-diol), effectively deactivating biological action of DHT.<ref name="x">{{cite journal|doi=10.1210/en.2002-0032|doi-access=free|date=1 July 2003|title=Human Type 3 3α-Hydroxysteroid Dehydrogenase (Aldo-Keto Reductase 1C2) and Androgen Metabolism in Prostate Cells|journal=Endocrinology |volume=144 |issue=7 |pages=2922–2932 | vauthors = Rižner TL, Lin HK, Peehl DM, Steckelbroeck S, Bauman DR, Penning TM |pmid=12810547 }}</ref><ref name="pmid15212687">{{cite journal | doi=10.1186/1471-2407-4-27 | doi-access=free | title=Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma | date=2004 | journal=BMC Cancer | volume=4 | article-number=27 | pmid=15212687 | pmc=459223 | vauthors = Lewis MJ, Wiebe JP, Heathcote JG }}</ref><ref name="drugbank">{{cite web | url=https://go.drugbank.com/articles/A10070 | title=Human type 3 3alpha-hydroxysteroid dehydrogenase (Aldo-keto reductase 1C2) and androgen metabolism in prostate cells. | DrugBank Online | access-date=2024-04-17 | archive-date=2024-04-17 | archive-url=https://web.archive.org/web/20240417075132/https://go.drugbank.com/articles/A10070 | url-status=live }}</ref><ref name="y">{{cite journal|doi=10.1210/jcem.86.2.7216|doi-access=free|date=1 February 2001|title=Human Types 1 and 3 3α-Hydroxysteroid Dehydrogenases: Differential Lability and Tissue Distribution1|journal=The Journal of Clinical Endocrinology & Metabolism |volume=86 |issue=2 |pages=841–846 | vauthors = Dufort I, Labrie F, Luu-The V |pmid=11158055 }}</ref>
==Isozymes of aldo-keto reductase family 1 member C== {{AKR1CN}}
==References== {{Reflist}}
==External links== * {{UCSC gene info|AKR1C2}} <!-- {{PDB Gallery|geneid=1646}} -->{{Alcohol oxidoreductases}} {{Enzymes}} {{Portal bar|Biology|border=no}}
Category:EC 1.1.1
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